The first analyzed a large cohort of individuals with RA and determined that there was synergistic interaction between the PTPN22 s2476601 variant and the HLA-DRB1 shared epitope alleles in participants who were positive for both antibodies to cyclic citrullinated peptides and antibodies to citrullinated α-enolase (49). This evidence concerns the gene HLA-DRB1 and rheumatoid arthritis.